It is clear that mutation cannot be understood in molecular terms without a detailed knowledge of the base sequence and structure of the genes involved. A prerequisite for this type of analysis is physical isolation of the genes of interest. Our initial effort has been directed toward the isolation of the human ribosomal cistrons (the genes which code for ribosomal RNA). Isolation and characterization of these cistrons should provide a substrate for analyzing the interaction of these genes with chemical mutagens and carcinogens and allow a detailed map of "hot spots" within these sequences. In addition the experience will provide approaches for isolating other genes from human DNA.